Pancreatic fibrosis is a pronounced histopathological feature of chronic pancreatitis, which is an active dynamic process resulting in irreversible tissue scarring and morphological alteration of the pancreatic parenchyma. The long-standing or recurrent inflammation of the pancreas is often associated with progressive fibrosis; thus, causes patients persistent abdominal pain and permanent impairment of pancreatic functions, and eventually leads to various systemic complications, including malabsorption and diabetes. According to a number of recent studies, pancreatic stellate cells (PSCs) play a critical role in the development of pancreatic fibrogenesis which is often accompanied with chronic pancreatitis and desmoplastic reaction of pancreatic cancer [Patel M and Fine D R 2005]. Typically, PSCs localized in the periacinar region of the exocrine pancreas are quiescent in normal condition. Upon injury or inflammation, these PSCs tend to lose their fat-droplets and transform into myofibroblast-like phenotype which can be identified with the presence of α-smooth muscle actin (α-SMA or Acta2) [Apte et al 1998]. The formation of these fibrotic stress filaments actually elicits the cascade of tissue repairing mechanisms in response to pro-fibrotic or pro-inflammatory mediators such as transforming growth factor-beta (TGF-β) generated against tissue injury [Apte et al 2004; Yoo B M et al 2005]. Once the PSCs are activated, they produce massive extracellular matrix (ECM) proteins, namely fibronectin 1 (FN1) and type I collagen, for the purpose of tissue repairing as well as regeneration [Schneider E et al 2001]. In fact, properties of stellate cells in the pancreas are similar to those present in other organs such as liver, kidney and lung. The overwhelmed production of ECM in an organ causes scarring of the parenchyma and leads to permanent morphological damages of the organ. Progressive fibrosis probably results in anatomical anomalies and organ failure. In the pancreas, the fibrotic condition may eventually lead to pancreatic exocrine and/or endocrine insufficiency. Therefore, the abolishment of the PSC activation is crucial to the treatment of chronic pancreatitis, explicitly fibrogenesis and the associated impairments of pancreatic functions, including pancreatogenic diabetes, also known as Type 3c diabetes milieus (T3cDM). Recent clinical data indicates that about 80% of T3cDM cases are arisen from chronic pancreatitis whereas 30-50% of chronic pancreatitis patients develop diabetes as the disease progresses [Ewald N and Hardt P D. 2013].
It is an objective of the present invention to provide a method of using dihydro-resveratrol as an anti-fibrotic agent in a subject.
Citation or identification of any reference in this section or any other section of this application shall not be construed as an admission that such reference is available as prior art for the present application.